The Brachyury gene was initially cloned from mouse developmental mutants characterized by an arrest in mesoderm formation (Heimann et al, Nature 1990; 343:617-22) has been recognized as gene that is important in mesoderm development during gastrulation. Brachyury is a member of a family of transcription factors, designated T-box transcription factors; these factors are characterized by a conserved DNA-binding domain (Papaioannou et al., Bioessays 1998; 20:9-19). These transcription factors play an essential role in the formation and organization of mesoderm in vertebrates (see, for example, Edwards et al., Genome Res 1996; 6:226-33). In addition to the important role of the T-box proteins in the control of developmental processes, several members of this family are deregulated in cancer. For example, the human Tbx2 gene has been reported to be amplified in pancreatic cancer cell lines (Mahlamaki et al., Genes Chromosomes Cancer 2002; 35:353-8) and is overexpressed in BRCA-1- and BRCA-2-mutated breast tumors (Sinclair et al., Cancer Res 2002; 62:3587-91). In addition, Tbx3 expression has been shown to be augmented in certain human breast cancer cell lines (Fan et al., Cancer Res 2004; 64:5132-9). Expression of Brachyury has also been documented in human teratocarcinoma lines: a subset of germ cell tumors, teratocarcinomas are embryonal carcinoma cells with competence for mesoderm differentiation (Gokhale et al., Cell Growth Differ 2000; 11:157-62) and in chordomas (see, for example, Vojovic et al., J Pathol 2006; 209:157-65). Brachyury also is overexpressed in a variety of human carcinomas, including breast, lung, colon, prostate and hepatocellular carcinoma and in malignancies of B-cell origin, such as chronic lymphocytic leukemia (CLL), B-cell lymphomas and Multiple Myeloma, among others.
Immunotherapeutic interventions against cancer depend on the identification of tumor antigens able to elicit a host immune response against the tumor cells. Good targets are molecules that are selectively expressed by malignant cells and that are also essential for malignant transformation and/or tumor progression. A need remains for reagents that induce an effective immune response to cancer, including a CD4 and a CD8 T cell response.